There are several trends in lung cancer patient management, all leading to an increase in the number of patients being treated with stereotactic body radiotherapy (SBRT). The trends are: (1) increased lung cancer detection through screening programs; (2) promising results of lung SBRT trials using current techniques and technology; and (3) comparable results of SBRT to surgery for medically operable patients leading to open phase II and III trials. Lung SBRT is an emerging technique utilizing high precision and large radiation doses to ablate lung tumor tissue. Despite excellent local control in most studies, the cost of using ablative radiation doses with current radiotherapy technology is morbidity, and in some cases mortality. The research proposed for this grant aims to significantly reduce the toxicity of lung SBRT through several technological developments and associated investigations. First we will solve the four-dimensional constrained treatment planning problem in collaboration with optimization experts; improved treatment plans will be created by including anatomic changes with time as an additional degree of freedom in the optimization. Second, we will combine two intra-treatment imaging modalities, external and internal, to obtain a real-time estimate of the target motion throughout the radiation treatment. Third, this position estimate will be used to direct beams of intensity modulated radiation to moving tumors in real time to offer unprecedented treatment conformality and normal tissue dose reduction. Fourth, a respiratory audiovisual biofeedback tool will be developed in collaboration with a musician and design expert. This tool will improve respiratory regularity for lung SBRT patients and thus decreasing PET/CT artifacts and target delineation errors on PET/CT scans and facilitating improved treatment beam-tumor alignment during radiation delivery. Such a comprehensive and multidisciplinary approach to manage tumor motion will offer the radiation oncology team superior radiation beam-tumor targeting and conformality methods to treat early stage lung cancer patients. We expect the research will ultimately result in a measurable improvement in treatment outcome and have a widespread impact on lung cancer management. PUBLIC HEALTH RELEVANCE: Lung stereotactic body radiotherapy (SBRT) is an increasingly used treatment for early stage lung cancer due to promising local control and survival rates. However, morbidity, and in some cases mortality, result using current technology. This comprehensive, multidisciplinary research program will develop improved treatment planning, image guidance and treatment delivery methods to offer unprecedented radiation beam-tumor targeting. Consequently the amount of healthy tissue irradiated and associated treatment toxicity will be reduced, resulting in improved health of lung cancer patients.